Human skin color is determined primarily by the content of the pigment melanin in the basal epidermis layer. Melanin is synthesized by the process of melanogenesis within melanocytes (pigment-producing cells). Melanin is deposited onto melanosomes, which are transferred to keratinocytes in the basal epidermal layer. Melanosomes present in these basal keratinocytes are the key determinants of skin color. The keratinocytes leave the basal layer and undergo differentiation forming the cornified top layer of the skin. Once the keratinocytes leave the basal layer, the melanosomes lose their characteristic electron dense structure, and the load of melanin is carried to the surface of the skin by the differentiating keratinocytes.
The skin can become hyperpigmented when too much melanin concentrates at one area or portion of the skin due to the retention time of the melanosomes in the basal layer. Hyperpigmentation can also occur as a result of overexposure to the sun or other inflammatory stimuli. Hyperpigmentation can take the form of solar lentigines (age spots), ephilides (freckles), melasma, chloasma, and pigmented keratoses.
The prior art discloses ways to treat hyperpigmentation by application of skin lightening agents. Representative skin lightening agents include hydroquinone and Vitamin C. Such agents typically lighten the skin by inhibiting the expression of tyrosinase enzymes. Tyrosinase is a major enzyme involved in the synthesis of melanin in melanosome cells of humans and mice. Its activity is linked to, for example, hair and skin pigmentation, and hyperpigmentation, age spots, and uneven skin coloration.
A powerful tool used to study gene function in mammalian cells is the process of small interfering RNA (siRNA)-mediated gene silencing. siRNA gene silencing is directly related to the process of RNA interference (RNAi) that is currently being done in Caenorhabditis elegans species of nematode. The process uses double-stranded RNA that is less than 30 base pairs long, and has a sequence complementary to the messenger RNA (mRNA) targeted. As the siRNA crosses the plasma membrane, the reaction of the cell is to destroy the siRNA and any sequence exactly like it. Native mRNA will also be destroyed by the cell when the siRNA code is the same as a specific region found on the native mRNA. Thus, the siRNA “silences” expression of a gene product by specifically destroying its mRNA. Numerous groups describe methods of specifically targeting a variety of endogenously and exogenously expressed genes using siRNA. (Brummelkamp et al. (2002) Science, 296: 550-553; Elbashir et al. (2001) Nature, 411: 494-498; Paul et. al. (2002) Nature Biotech., 20:505-508; and Hannon, P. (2002) Nature, 418: 244-251). Gene silencing technology is also being applied in a broad range of therapeutic applications.
Safe, effective and new compositions containing siRNA oligomers to treat, prevent, reduce, inhibit, and/or improve hyperpigmentation, or other unwanted pigmentation in skin and hair, would be advantageous for the formulation of treatments and products for the skin. As described herein, novel and beneficial methods and compositions, as well as their mode of action, for the treatment of hyperpigmentation, or other unwanted pigmentation and the like, as well as for personal care products for the skin, are provided by the present invention.